{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:38:14Z","timestamp":1790642294072,"version":"4.1.0"},"reference-count":36,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2023,2,23]],"date-time":"2023-02-23T00:00:00Z","timestamp":1677110400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007301","name":"Harvard University Center for AIDS Research","doi-asserted-by":"crossref","award":["P30 AI060354"],"award-info":[{"award-number":["P30 AI060354"]}],"id":[{"id":"10.13039\/100007301","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000865","name":"Sub-Saharan African Network for TB\/HIV Research Excellence","doi-asserted-by":"publisher","award":["INV-033558"],"award-info":[{"award-number":["INV-033558"]}],"id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Institutes of Health NIH Fogarty International Center","award":["K43 TW012350-01"],"award-info":[{"award-number":["K43 TW012350-01"]}]},{"name":"National Institutes of Health NIH\/ National Institute of Allergy and Infectious Diseases","award":["NIH K24 AI131928"],"award-info":[{"award-number":["NIH K24 AI131928"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>Women living with HIV-1 (WLHIV) are at higher risk of having an adverse birth outcome, but the underlying mechanism(s) are unknown. We hypothesized that HIV-associated endothelial activation could adversely impact placental function and lead to impaired fetal growth or stillbirth.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>We used stored samples from WLHIV and HIV-negative women who had enrolled during pregnancy in the observational Botswana <jats:italic>Tshipidi<\/jats:italic> cohort. Written informed consent was obtained from the participants. We measured plasma levels of markers of endothelial activation (soluble vascular adhesion molecule 1 [VCAM-1], intercellular adhesion molecule 1 [ICAM-1] and E-selectin) from samples taken during pregnancy. We compared log<jats:sub>10<\/jats:sub> biomarker levels by maternal HIV status and by the timing of ART initiation (ART prior to conception vs. during pregnancy; ART prior to sample collection vs. no ART prior to sampling) using t-tests and the Kruskal-Wallis rank test. We evaluated the association between these biomarkers and adverse birth outcomes (composite of stillbirth or small for gestational age [SGA]) using univariate and multivariate log-binomial regression controlling for maternal age (continuous) and timing of ART start. We also used generalized linear models (GLM) to evaluate the association between continuous birthweight (in grams) and gestational age (in weeks) and markers of endothelial dysfunction, adjusting for maternal age (continuous) and timing of ART relative to sample collection.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>Specimens collected before delivery were available for 414 women (372 WLHIV and 42 HIV-negative women), with a median age of 28 years and median gestational age at sample collection of 30 weeks (range 26, 35 weeks). WLHIV had significantly higher median VCAM1 (p = 0.002) than HIV-negative women, but HIV-negative women had higher median ICAM1 (p = 0.01); e-Selectin levels did not differ by maternal HIV status. Women starting ART during pregnancy had higher log<jats:sub>10<\/jats:sub> VCAM1 levels than those on ART before conception, regardless of whether the sample was collected before (p = 0.02) or after (p = 0.03) ART initiation. However, ICAM1 and e-Selectin did not differ significantly by ART status or ART timing. Ninety-eight women (91 WLHIV and 7 HIV-negative), or 9 (2%) and 89 (22%) included in this study, had a stillborn or SGA baby respectively. Univariate and adjusted analyses did not show significant associations between levels of any of the biomarkers with these adverse birth outcomes. However, lower birthweight (p = 0.03) and lower gestational age at delivery were associated e-Selectin and ICAM (p = 0.008), respectively.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusion<\/jats:title>\n<jats:p>Maternal HIV infection and lack of ART (or recent ART initiation) were associated with one marker of greater endothelial activation (VCAM-1), but not with other markers (ICAM-1 nor E-selectin) in pregnancy. e-Selectin was associated with lower birthweight and every unit increase in log ICAM-1 at delivery was associated with lower gestation age at delivery.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0281910","type":"journal-article","created":{"date-parts":[[2023,2,23]],"date-time":"2023-02-23T18:31:06Z","timestamp":1677177066000},"page":"e0281910","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":9,"title":["Maternal biomarkers of endothelial dysfunction and pregnancy outcomes in women with and without HIV in Botswana"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2388-9637","authenticated-orcid":true,"given":"Gaerolwe","family":"Masheto","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sikhulile","family":"Moyo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Terence","family":"Mohammed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Banda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlene","family":"Raphaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gloria","family":"Mayondi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Makhema","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roger","family":"Shapiro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mosepele","family":"Mosepele","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Zash","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shahin","family":"Lockman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2023,2,23]]},"reference":[{"key":"pone.0281910.ref001","unstructured":"World Health Organization (WHO) \u2019Mother-to-child transmission of HIV\u2019; c2021. Available from: https:\/\/www.who.int\/teams\/global-hiv-hepatitis-and-stis-programmes\/hiv\/prevention\/mother-to-child-transmission-of-hiv."},{"issue":"7","key":"pone.0281910.ref002","first-page":"CD003510","article-title":"Antiretrovirals for reducing the risk of mother-to-child transmission of HIV infection","author":"N Siegfried","year":"2011","journal-title":"Cochrane Database Syst Rev"},{"issue":"11","key":"pone.0281910.ref003","first-page":"1715","article-title":"No perinatal HIV-1 transmission from women with effective antiretroviral therapy starting before conception","volume":"61","author":"L Mandelbrot","year":"2015","journal-title":"Clin Infect Dis"},{"issue":"2","key":"pone.0281910.ref004","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/j.ijgo.2014.05.024","article-title":"HIV and maternal mortality","volume":"127","author":"E Lathrop","year":"2014","journal-title":"Int J Gynaecol Obstet"},{"issue":"7","key":"pone.0281910.ref005","doi-asserted-by":"crossref","first-page":"1051","DOI":"10.1093\/infdis\/jiv390","article-title":"Antiretroviral Therapy and Adverse Pregnancy Outcome: The Elephant in the Room?","volume":"213","author":"LM Mofenson","journal-title":"J Infect Dis"},{"issue":"11","key":"pone.0281910.ref006","doi-asserted-by":"crossref","first-page":"1695","DOI":"10.1093\/infdis\/jis553","article-title":"Highly active antiretroviral therapy and adverse birth outcomes among HIV-infected women in Botswana","volume":"206","author":"JY Chen","journal-title":"J Infect Dis"},{"issue":"7","key":"pone.0281910.ref007","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.1093\/infdis\/jiv389","article-title":"Antiretroviral Therapy in Relation to Birth Outcomes among HIV-infected Women: A Cohort Study","volume":"213","author":"N Li","year":"2016","journal-title":"J Infect Dis"},{"issue":"18","key":"pone.0281910.ref008","doi-asserted-by":"crossref","first-page":"1726","DOI":"10.1056\/NEJMoa1511691","article-title":"Benefits and Risks of Antiretroviral Therapy for Perinatal HIV Prevention","volume":"375","author":"MG Fowler","year":"2016","journal-title":"N Engl J Med"},{"issue":"7","key":"pone.0281910.ref009","doi-asserted-by":"crossref","first-page":"e804","DOI":"10.1016\/S2214-109X(18)30218-3","article-title":"Comparative safety of dolutegravir-based or efavirenz-based antiretroviral treatment started during pregnancy in Botswana: an observational study","volume":"6","author":"R Zash","year":"2018","journal-title":"Lancet Glob Health"},{"key":"pone.0281910.ref010","unstructured":"Chi1 BH, Farhad M, Owor M, Chipato T, Qin M, Dadabhia S, et al. Antenatal antiretroviral therapy and adverse birth outcomes: the PROMISE trial. Poster abstract 776. Available at: http:\/\/www.croiconference.org\/sessions\/antenatal-antiretroviral-therapy-and-adverse-birth-outcomes-promise-trial (abstract and poster)."},{"key":"pone.0281910.ref011","unstructured":"Prevention of mother-to-child transmission Estimates by WHO region, c2016. Available at: https:\/\/apps.who.int\/gho\/data\/view.main.23500REG."},{"key":"pone.0281910.ref012","article-title":"Preterm Birth: Causes, Consequences, and Prevention","author":"Institute of Medicine (US) Committee on Understanding Premature Birth and Assuring Healthy Outcomes","year":"2007"},{"issue":"11","key":"pone.0281910.ref013","doi-asserted-by":"crossref","first-page":"1695","DOI":"10.1093\/infdis\/jis553","article-title":"Highly active antiretroviral therapy and adverse birth outcomes among HIV-infected women in Botswana","volume":"206","author":"JY Chen","year":"2012","journal-title":"J Infect Dis"},{"issue":"4","key":"pone.0281910.ref014","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1097\/QAI.0000000000000847","article-title":"Reassuring Birth Outcomes with Tenofovir\/Emtricitabine\/Efavirenz Used for Prevention of Mother-to-Child Transmission of HIV in Botswana","volume":"71","author":"R Zash","year":"2016","journal-title":"J Acquir Immune Defic Syndr"},{"issue":"7","key":"pone.0281910.ref015","doi-asserted-by":"crossref","first-page":"2506","DOI":"10.1210\/jc.2006-2190","article-title":"Increased acute myocardial infarction rates and cardiovascular risk factors among patients with human immunodeficiency virus disease","volume":"92","author":"VA Triant","journal-title":"J Clin Endocrinol Metab"},{"issue":"5","key":"pone.0281910.ref016","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1212\/WNL.0b013e31820a0cfc","article-title":"Increasing incidence of ischemic stroke in patients with HIV infection","volume":"76","author":"B Ovbiagele","year":"2011","journal-title":"Neurology"},{"issue":"4","key":"pone.0281910.ref017","first-page":"676","article-title":"Cardiovascular disease in HIV: traditional and nontraditional risk factors","volume":"22","author":"SK Grinspoon","year":"2014","journal-title":"Top Antivir Med"},{"issue":"8","key":"pone.0281910.ref018","doi-asserted-by":"crossref","first-page":"1228","DOI":"10.1097\/QAD.0b013e328339192f","article-title":"Increased risk of myocardial infarction in HIV-infected patients in France, relative to the general population","volume":"24","author":"S Lang","year":"2010","journal-title":"AIDS"},{"issue":"1","key":"pone.0281910.ref019","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1161\/01.STR.0000043821.35051.FA","article-title":"Stroke in black South African HIV-positive patients: a prospective analysis","volume":"34","author":"A Mochan","year":"2003","journal-title":"Stroke"},{"issue":"16","key":"pone.0281910.ref020","doi-asserted-by":"crossref","first-page":"1146","DOI":"10.1136\/heartjnl-2012-303177","article-title":"Recent advances in HIV-associated cardiovascular diseases in Africa","volume":"99","author":"FF Syed","year":"2013","journal-title":"Heart"},{"issue":"6","key":"pone.0281910.ref021","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1097\/COH.0b013e32833ed7ec","article-title":"Biomarkers and HIV-associated cardiovascular disease","volume":"5","author":"JV Baker","year":"2010","journal-title":"Curr Opin HIV AIDS"},{"issue":"3","key":"pone.0281910.ref022","first-page":"183","article-title":"Endothelial dysfunction: cardiovascular risk factors, therapy, and outcome","volume":"1","author":"HA Hadi","year":"2005","journal-title":"Vasc Health Risk Manag"},{"issue":"9096","key":"pone.0281910.ref023","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/S0140-6736(97)09032-6","article-title":"Plasma concentration of soluble intercellular adhesion molecule 1 and risks of future myocardial infarction in apparently healthy men","volume":"351","author":"PM Ridker","year":"1998","journal-title":"Lancet"},{"issue":"2","key":"pone.0281910.ref024","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1016\/S0735-1097(00)00742-7","article-title":"Plasma concentration of soluble vascular cell adhesion molecule-1 and subsequent cardiovascular risk","volume":"36","author":"JA de Lemos","year":"2000","journal-title":"J Am Coll Cardiol"},{"issue":"10","key":"pone.0281910.ref025","doi-asserted-by":"crossref","first-page":"ofaa425","DOI":"10.1093\/ofid\/ofaa425","article-title":"Endothelial Dysfunction Is Related to Monocyte Activation in Antiretroviral-Treated People with HIV and HIV-Negative Adults in Kenya","volume":"7","author":"TM Temu","year":"2020","journal-title":"Open Forum Infect Dis"},{"issue":"3","key":"pone.0281910.ref026","doi-asserted-by":"crossref","first-page":"155","DOI":"10.5830\/CVJA-2018-003","article-title":"HIV disease is associated with increased biomarkers of endothelial dysfunction despite viral suppression on long-term antiretroviral therapy in Botswana","volume":"29","author":"M Mosepele","year":"2018","journal-title":"Cardiovasc J Afr"},{"issue":"1","key":"pone.0281910.ref027","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3233\/BIR-2011-0579","article-title":"Biomechanics of leukocyte rolling","volume":"48","author":"P Sundd","year":"2011","journal-title":"Biorheology"},{"issue":"1","key":"pone.0281910.ref028","doi-asserted-by":"crossref","first-page":"e85716","DOI":"10.1371\/journal.pone.0085716","article-title":"Maternal biomarkers of endothelial dysfunction and preterm delivery","volume":"9","author":"X Chen","year":"2014","journal-title":"PLoS One"},{"issue":"4","key":"pone.0281910.ref029","doi-asserted-by":"crossref","first-page":"e20170988","DOI":"10.1542\/peds.2017-0988","article-title":"Neurodevelopment of HIV-Exposed and HIV-Unexposed Uninfected Children at 24 Months","volume":"140","author":"S Chaudhury","year":"2017","journal-title":"Pediatrics"},{"key":"pone.0281910.ref030","unstructured":"ELISA Guide\u2013BioSystems. Available at: www.biosystems.com.ar \u2013R & D systems-elisa-guide-br2.pdf."},{"issue":"9946","key":"pone.0281910.ref031","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1016\/S0140-6736(14)60932-6","article-title":"International Fetal and Newborn Growth Consortium for the 21st Century (INTERGROWTH-21st). International standards for newborn weight, length, and head circumference by gestational age and sex: the Newborn Cross-Sectional Study of the INTERGROWTH-21st","volume":"384","author":"J Villar","year":"2014","journal-title":"Project. Lancet"},{"issue":"10021","key":"pone.0281910.ref032","doi-asserted-by":"crossref","first-page":"844","DOI":"10.1016\/S0140-6736(16)00384-6","article-title":"INTERGROWTH-21st Consortium. 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Available at: http:\/\/atlasgeneticsoncology.org\/Genes\/ICAM1ID40909ch19p13.html."},{"issue":"3","key":"pone.0281910.ref034","doi-asserted-by":"crossref","first-page":"H926","DOI":"10.1152\/ajpheart.00779.2008","article-title":"ICAM-1: role in inflammation and in the regulation of vascular permeability","volume":"295","author":"PG Frank","year":"2008","journal-title":"Am J Physiol Heart Circ Physiol"},{"issue":"6","key":"pone.0281910.ref035","first-page":"495","article-title":"Wystepowanie miedzykom\u00f3rkowej czastki adhezyjnej-1 (ICAM-1) na powierzchni limfocyt\u00f3w krwi obwodowej ciezarnych z nadci\u015bnieniem indukowanym ciaza [Expression of intercellular adhesion molecule-1 (ICAM-1) on the surface of peripheral blood lymphocytes of pregnant women with pregnancy-induced hypertension]","volume":"73","author":"JR Wilczy\u0144ski","year":"2002","journal-title":"Ginekol Pol"},{"issue":"5","key":"pone.0281910.ref036","doi-asserted-by":"crossref","first-page":"688","DOI":"10.3346\/jkms.2004.19.5.688","article-title":"Maternal serum levels of VCAM-1, ICAM-1 and E-selectin in preeclampsia","volume":"19","author":"SY Kim","year":"2004","journal-title":"J Korean Med Sci"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0281910","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,23]],"date-time":"2023-02-23T18:31:25Z","timestamp":1677177085000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0281910"}},"subtitle":[],"editor":[{"given":"Ashish","family":"K. 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